Causes of Deceased Donors Loss before Organ Retrieval.

Background
When potential brain dead donors are in line-up for organ retrieval, their loss would be such a disaster. The aim of this study was to detect the occurrence of different disorders leading to pre-retrieval donor's cardiac arrest and loss in order to prevent this energy and money wasting challenge.


Materials and Methods
In this observational study, medical records of potential donors from 2001 to 2016 who were lost after transfer to Organ Procurement Unit (OPU) of Masih Daneshvari Hospital and before organ donation were reviewed and weigh of every responsible disorder was tested. Equal number of actual organ donors were randomly selected others for comparison.


Results
In 14 years of experience in organ donation, 46 (3.09%) out of 1485 potential donors were lost after their transfer to OPU with the aim of organ donation. Mean age of donors and their gender were not significantly different to actual donors (37.4 ± 17.7 versus 39.2 ± 18.4, P= 0.2). However, proportion of drug toxicity as the cause of brain death was more common in the lost donors (19.5 versus 5.3%, P= 0.001). Thirteen (28.2%) of the cases had a documented history of ischemic heart disease, which was not as common in actual donors. After excluding hypotension and diabetes insipidus, more incident disorders among the lost donors were metabolic acidosis, hypocalcaemia, hyperglycemia, thrombocytopenia, severe anemia and different presentations of coagulopathy. Clinical conditions of 47.8% of cases were flared up by different severities of acute kidney injury and mean ALT levels were significantly higher than actual donors. All the above mentioned disorders were significantly more common in lost donors than actual ones.


Conclusion
Drug toxicity, history of ischemic heart disease and occurrence of acute kidney injury are associated with more potential donors' loss before organ retrieval.


INTRODUCTION
Transplantation is still the last rescue treatment for many solid organ end-stage diseases (1). Currently, the best accessible and acceptable sources of these organs are deceased donors. However, unprecedented scarcity of transplantable organs have solicited enhanced effort to expand donor pool (2). Critical management of brain-dead al. discovered that 10-20% of patients undergoing catecholamine storm in the course of brain death would be facing cardiac arrest before full-blown loss of brain function (5). Therefore, circulatory survivors will get severe harmful assaults from the process which can cause metabolic, hematologic and coagulation disorders as well as fluid and electrolyte disturbances (6) before organ retrieval. Loss of pituitary function can lead to Antidiuretic Hormone (ADH) insufficiency and Diabetes Insipidus (DI).
The latter situation would cause polyuria, hypernatremia and other electrolyte imbalances besides arterial hypotension due to loss of intravascular volume (7). Lack of thermoregulation and the consequent hypothermia would be accompanied by metabolic acidosis and coagulopathy (8). Being prone to infectious agents, the potential donors may develop sepsis (9). Hormonal insufficiency might lead to inappropriate metabolism of organs and circulatory collapse (9). The above mentioned conditions as well as many other ICU-associated complications can result in making the efforts of organ donation process in vain.
When potential brain dead donors are in line-up for organ retrieval, their loss would be such a disaster to come.
The aim of this study was to detect and evaluate the occurrence of different disorders leading to pre-retrieval donor's cardiac arrest and loss in order to prevent this energy and money wasting challenge.

MATERIALS AND METHODS
In the 14 years of organ donation practice from 2003 to 2016, when primary diagnosis was made, potential donors got transferred by an ambulance from the original caregiver hospital to ICU of Organ Procurement Unit (OPU) of Masih Daneshvari Hospital. While completion of formal process of brain death certification and obtaining donation consent from next of kin, medical management of the donor continued to dispel laboratory abnormalities as well as clinical casualties. Demographic data (age and sex), history of any disease such as ischemic heart disease or organ failure, cause of brain death, type of misused agent in case of drug toxicity, any drugs administered in treatment process, hospitalization and intubation period, and need for inotropic agents were among the provided record for every donor. Prevalence of hypo/hypertension, electrolyte disturbances (Sodium, Calcium, Potassium, Magnesium, and Phosphate), DI metabolic disorders (acidosis or alkalosis), hematologic disorders (anemia, thrombocytopenia, and leukopenia/cytosis), coagulopathy or renal/liver failure were recorded.
In this retrospective study, the above factors and abnormalities were compared between the potential donors who were lost before organ retrieval surgery to 46 actual donors (equal quantity). The compared groups were selected randomly from list of donors regarding their age.
With every lost potential donor, an actual one was selected with ±2 years as the accepted difference. Among the equivalent cases, one of them was randomly selected.
Statistical analyses were performed, by SPSS software version 23. The quantitative data was reported as mean ± standard deviation (SD). The nominal variables were presented as percentages. Subsequently, student's sample t-test or Chi-square with significance set at (P ≤ 0.05) was used to analyze the data.    Gramm et al. found 78% of cases to be suffering from DI (19). As mentioned before, these two disorders have been proven to occur in all experimental brain death models.

RESULTS
One possible explanation may be the fact that some other human based studies considering lower occurrence of the conditions have included all brain-dead cases who may or may not become organ donors. As opposed to, we observed final candidates for organ donation. Therefore we were facing full-blown progress of brain death because we took time for donor management.
Acute Kidney Injury (AKI), liver function tests abnormalities and acute respiratory distress syndrome which is defined by low PaO2/FIO2 as well as clinical criteria, were observed more in lost donors. The findings regarding high mortality rate of ICU hospitalized patients with organ failure is not new (20)(21)(22). In our insight, donors with single transplantable organs are more prone to irreversible cardiac arrest and loss. The fact defines need for more prompt management protocols for these potential donors.

CONCLUSION
Drug toxicity as the cause of brain death, history of ischemic heart disease and occurrence of acute kidney injury and liver and lung dysfunction are associated with more potential donors' loss before organ retrieval.
Metabolic acidosis, hyperglycemia, hypocalcaemia and coagulopathy are more common in unsuccessful organ donation effort. As a result, implementation of proper management guidelines, especially regarding these abnormalities is recommended.